For the past several years we have been designing and evaluating new iron chelating compounds for the treatment of patients with Beta-thalassemia major. Two methods are used identify useful agents: 1.) an in vivo assay using iron overloaded rats prepared by hypertransfusion with rat blood and 2.) the use of Chang liver cells cultured in vitro. In the past year we evaluated 26 benzoic acid derivatives. None appear to be more effective than 2-3-dihydroxybenzoic acid which had been identified earlier. We are currently synthesizing multidentate ligands containing 2-3-dihydroxybenzoyl moieties. In a study of hydroxamic molecules we have identified rhodotorulic acid as a potentially useful compound. This compound, we believe, has promise because of its decreased water solubility which should make possible its administration as a suspension which would slowly dissolve and enter the circulation over a prolonged period. Hopefully, this pharmacological property will allow it to remove iron from the chelatable pools as they appear to refill upon depletion. We have recently identified another hydroxamic acid derivative, cholylhydroxamic acid, as potentially useful. Initial experiments in iron overloaded rats indicate that oral administration led to fecal excretion of iron. Presently this compound is undergoing further pharmacological and toxicological evaluation. BIBLIOGRAPHIC REFERENCES: White GP, Jacobs A, Grady RW & Cerami A: The use of Chang cells cultured in vitro to evaluate potential iron chelating drugs. Brit J Haematol 33: 487-495, 1976. Jones RL, Peterson CM, Grady RW, Kumbaraci T, Graziano JH & Cerami A: Effects of iron chelators and iron overload on salmonella infection. Nature, in press 1977.